3-Deazaadenosine--an inhibitor of interleukin 1 production by human peripheral blood monocytes.
3-Deazaadenosine (c3Ado) has been reported to have properties of an immunosuppressive and anti-inflammatory agent. This study was designed to investigate whether c3Ado might exert anti-inflammatory activities through inhibiting Interleukin 1 (IL-1). c3Ado was found to be a potent inhibitor of IL-1 production by LPS stimulated human peripheral blood monocytes and acted at the level of synthesis rather than secretion. c3Ado also had direct effects on IL-1 biological activity in two separate assays; thymocyte proliferation and induction of prostaglandin release. Further experiments indicated that c3Ado also inhibited growth factor dependent proliferation driven by both Interleukin-2 and Interleukin-3 as well as the proliferation of a number of non-growth factor dependent cells. However, short term exposure to c3Ado resulted in no inhibition of 3H-thymidine incorporation by cells but a significant inhibition of 3H-uridine uptake into TCA precipitable material. These results suggest that c3Ado is a selective inhibitor of RNA synthesis and inhibits IL-1 production and activity by blocking new messenger RNA production induced by LPS or IL-1. General inhibition of RNA synthesis would also account for its anti-proliferative activity.
Schmidt
J A
JA
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, Kent, U.K.
Bomford
R
R
Gao
X M
XM
Rhodes
J
J
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D008715:Methionine / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D014238:Trichloroacetic Acid; D014372:Tubercidin / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D013462:Sulfur Radioisotopes; C018258:3-deazaadenosine; D014238:Trichloroacetic Acid; D008715:Methionine; D014372:Tubercidin